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Population Pharmaco...
Population Pharmacokinetic and Pharmacodynamic Modeling of Artemisinin Resistance in Southeast Asia
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- Lohy Das, Jesmin, 1979- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics Research Group
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- Dondorp, Arjen M. (författare)
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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- Nosten, Francois (författare)
- Shoklo Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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- Aung, Pyae Phyo (författare)
- Shoklo Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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- Hanpithakpong, Warunee (författare)
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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- Ringwald, Pascal (författare)
- Drug Resistance and Containment, Global Malaria Programme, World Health Organization, Geneva, Switzerland
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- Lim, Pharath (författare)
- Medical care development international, Maryland, USA
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- White, Nicholas (författare)
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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- Karlsson, Mats O (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics Research Group
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- Bergstrand, Martin, 1977- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometric Research Group
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- Tarning, Joel (författare)
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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(creator_code:org_t)
- 2017-09-11
- 2017
- Engelska.
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Ingår i: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 19:6, s. 1842-1854
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Orally administered artemisinin-based combination therapy is the first-line treatment against uncomplicated P. falciparum malaria worldwide. However, the increasing prevalence of artemisinin resistance is threatening efforts to treat and eliminate malaria in Southeast Asia. This study aimed to characterize the exposure-response relationship of artesunate in patients with artemisinin sensitive and resistant malaria infections. Patients were recruited in Pailin, Cambodia (n = 39), and Wang Pha, Thailand (n = 40), and received either 2 mg/kg/day of artesunate mono-therapy for 7 consecutive days or 4 mg/kg/day of artesunate monotherapy for 3 consecutive days followed by mefloquine 15 and 10 mg/kg for 2 consecutive days. Plasma concentrations of artesunate and its active metabolite, dihydroartemisinin, and microscopy-based parasite densities were measured and evaluated using nonlinear mixed-effects modeling. All treatments were well tolerated with minor and transient adverse reactions. Patients in Cambodia had substantially slower parasite clearance compared to patients in Thailand. The pharmacokinetic properties of artesunate and dihydroartemisinin were well described by transit-compartment absorption followed by one-compartment disposition models. Parasite density was a significant covariate, and higher parasite densities were associated with increased absorption. Dihydroartemisinin-dependent parasite killing was described by a delayed sigmoidal Emax model, and a mixture function was implemented to differentiate between sensitive and resistant infections. This predicted that 84% and 16% of infections in Cambodia and Thailand, respectively, were artemisinin resistant. The final model was used to develop a simple diagnostic nomogram to identify patients with artemisinin-resistant infections. The nomogram showed > 80% specificity and sensitivity, and outperformed the current practice of day 3 positivity testing.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Populationsbiologi
- Population Biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Lohy Das, Jesmin ...
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Dondorp, Arjen M ...
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Nosten, Francois
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Aung, Pyae Phyo
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Hanpithakpong, W ...
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Ringwald, Pascal
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Lim, Pharath
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White, Nicholas
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Karlsson, Mats O
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Bergstrand, Mart ...
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Tarning, Joel
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AAPS Journal
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Uppsala universitet